2023+循证共识：反流样症状患者的管理建议（英文版pdf

Review0954-691X Copyright 2023 The Author(s).Published by Wolters Kluwer Health,Inc.DOI:10.1097/MEG.0000000000002682 1Management advice for patients with reflux-like symptoms:an evidence-based consensusA.PaliHungina,RenaYadlapatib,FoteiniAnastasiouc,Albert J.Bredenoordd,HashemEl Serage,PierluigiFracassof,Juan MMendiveg,Edoardo V.Savarinoh,DanielSifrimi,MihaelaUdrescuj and Peter JKahrilaskPatients with reflux-like symptoms(heartburn and regurgitation)are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes,lifestyle modifications,behavioural changes or fast-acting rescue therapies.One reason for this may be the lack of emphasis in management guidelines owing to low-quality evidence and a paucity of interventional studies.Thus,a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus.A steering committee selected topics for literature searches using the PubMed database,and a modified Delphi process including two online meetings and two rounds of voting was conducted to generate consensus statements based on prespecified criteria(67%voting strongly agree or agree with minor reservation).After expert discussion and two rounds of voting,21 consensus statements were generated,and assigned strength of evidence and Grades of Recommendation,Assessment,Development,and Evaluation(GRADE)rating.Eleven statements achieved the strongest(100%)agreement:five are related to diet and include identification and avoidance of dietary triggers,limiting alcohol,coffee and carbonated beverages,and advising patients troubled by postprandial symptoms not to overeat;the remaining six statements concern advice around smoking cessation,weight loss,raising the head-of-the-bed,avoiding recumbency after meals,stress reduction and alginate use.The aim of developing the consensus statements is that they may serve as a foundation for tools and advice that can routinely help patients with reflux-like symptoms better understand the causes of their symptoms and manage their individual risk factors and triggers.Eur J Gastroenterol Hepatol XXX:XXXXXXXXCopyright 2023 The Author(s).Published by Wolters Kluwer Health,Inc.IntroductionHeartburn and regurgitation are common symptoms,experienced regularly by up to 2050%of individuals 1,2.Individuals with mild heartburn frequently use over-the-counter antacids,while those with more severe symp-toms often resort to long-term use of acid-suppressant medications.This acid-centred approach,which is highly effective for healing reflux oesophagitis,ignores the more complex aetiology of oesophageal symptoms,wherein dietary habits,reflux hypersensitivity,psychosocial fac-tors and obesity,may also play a role 35.However,the impracticality of exploring this complex symptom aeti-ology compared with the pragmatic approach of using proton pump inhibitors(PPIs)has led to widespread,open-ended PPI use.Unfortunately,this also means that reflux-like symptoms,the severity of which exhibits only a weak relationship with pathological oesophageal acid exposure,continue to impact the day-to-day lives of a large proportion of individuals 1,6.The concept that dietary and lifestyle factors can influence the likelihood of reflux-like symptoms is well accepted.However,patients are generally given mini-mal(and inconsistent)advice about implementing diet,lifestyle and behavioural changes 710,despite these being low-harm,pragmatic approaches to self-manage-ment.One reason for this is a historical lack of emphasis in evidence-based clinical guidelines,which stems from a paucity of high-quality interventional studies.Ideally,guidelines and clinical advice should be based on rigorous European Journal of Gastroenterology&Hepatology XXX,XXX:XXXXXXXXKeywords:advice,brain-gut,diet,gastro-oesophageal reflux disease,lifestyle,oesophagus,symptomsaProfessor Emeritus,Population Health Sciences Institute,Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,UK,bDivision of Gastroenterology,University of California San Diego,La Jolla,California,USA,c4th Local Primary Care Team,Municipality Practice and Academic Practice of Heraklion;University of Crete,Crete,Greece,dDepartment of Gastroenterology,Amsterdam University Medical Centers,Amsterdam,the Netherlands,eDepartment of Medicine,Baylor College of Medicine,Houston,Texas,USA,fDepartment of Gastroenterology and Digestive Endoscopy,Ospedale Sandro Pertini,Local Health Agency Roma 2,Rome,Italy,gLa Mina Primary Care Academic Centre,Catalan Health Institute,University of Barcelona,Spain,hDepartment of Surgery,Oncology and Gastroenterology,University of Padua,Padua,Italy,iWingate Institute of Neurogastroenterology,Queen Mary University of London,London,UK,jIndividual Family Practice,Bucharest,Romania and kDivision of Gastroenterology,Feinberg School of Medicine,Northwestern University,Chicago,Illinois,USACorrespondence to Peter J Kahrilas,MD,Division of Gastroenterology,Feinberg School of Medicine,Northwestern University,NMH/Arkes Family Pavilion Suite 1400,676 N Saint Clair St,Chicago,Illinois 60611,USATel:[phone];e-mail:Received 23 August 2023 Accepted 11 October 2023.A.Pali Hungin and Rena Yadlapati shared co-first authorship.Supplemental Digital Content is available for this article.Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journals website,.This is an open-access article distributed under the terms of the Creative Com-mons Attribution-Non Commercial-No Derivatives License 4.0(CCBY-NC-ND),where it is permissible to download and share the work provided it is properly cited.The work cannot be changed in any way or used commercially without permission from the journal.2 European Journal of Gastroenterology&HepatologyXXX XXX Volume XXX Number 00evidence,for which randomised controlled trials(RCTs)are the gold standard.However,a lack of RCT evidence does not negate the value of lifestyle recommendations.Hence,the Delphi method,with greater emphasis on clin-ical experience and expert consensus,was used to develop a set of consensus statements of advice to help providers and patients target the physical and perceptual factors contributing to reflux-like symptoms.These statements can serve as a basis for facilitating doctor-patient commu-nication as well as aiding the development of self-manage-ment tools to better support the wellbeing of patients with reflux-like symptoms.MethodsStudy designThe consensus procedure was based on a literature review and rating of statements by an expert panel(summarised in Fig.1).Consensus statements were developed over the course of two online meetings and two rounds of voting.A meeting facilitator and medical writer attended the meet-ings and collated the results(Lumanity,UK).The steering committee,comprising two experienced gastroenterologists and a general practitioner with a spe-cialist interest in gastroenterology,defined key themes for literature searches and selected eight further panel members(five gastroenterologists and three primary care doctors)who were experienced in the management of reflux-like symptoms(average 28 years in practice,range 1345 years),and involved in gastroenterology research and education(held positions in national/regional gas-troenterological societies and/or have previously been involved in guideline development).The panel represented seven countries,including the USA,Italy,Spain,Greece,the Netherlands,Romania and the UK.Targeted literature searchesLiterature searches using the PubMed database were con-ducted in June 2022 by an information specialist using keywords identified by the steering committee to identify relevant publications(excluding editorials,commentary,consensus statements,case reports,letters and response papers)in English from 2002 to 2022.The search strings for terms in the title and abstract are shown in Fig.1.The terms infant,child,eosinophilic oesophagitis,Barretts,functional dyspepsia,gastroparesis,oesoph-ageal adenocarcinoma and Burning Mouth Syndrome were excluded.The reference lists of retrieved articles were used to identify any further studies of interest.Throughout the consensus process,panel members were also encouraged to contribute supporting evidence.Consensus procedureThe literature searches identified 406 articles.After the removal of 50 duplicates and the exclusion of nonrelevant studies,a total of 135 references were reviewed and used by the steering committee to develop 27 pilot statements around risk factors and interventions for reflux-like symp-toms(Supplemental digital content 1,http:/ pilot statements and supporting articles were shared with the expert panel together with the level of supporting evidence for each study which had been assigned by the steering committee using the scale(16),as described previously 11(Table 1).In the first consensus meeting,statements and evidence were reviewed and,based on panel discussion and agreement,three state-ments were added and four were eliminated(Supplemental digital content 1,http:/ revised pilot statements were then used as a basis for the steering committee to develop a set of 21 directive state-ments,which were shared(with supporting evidence)for anonymous voting using the Qualtrics online platform.For each statement,the experts,including the steering committee,indicated their level of agreement on a scale from 1 to 6(1=strongly disagree;2=disagree with major reservation;3=disagree with minor reservation;4=agree with major reservation;5=agree with minor reservation;and 6=strongly agree).Results were analysed by the meet-ing facilitator.The consensus threshold was set a priori as agreement(level 5 or 6)by at least 67%of respondents.During the second meeting,round one voting results were reviewed.Statements that did not reach consensus were discussed and revised and an additional statement was added ahead of a second round of voting.After the sec-ond round of voting,each of the consensus statements was assigned strength of evidence(AD)by the steering commit-tee and were rated using the Grades of Recommendation,Assessment,Development,and Evaluation(GRADE)sys-tem 12(high,moderate,low,very low,see Table 1).ResultsConsensus was achieved for 21 of the final 22 statements(Table 2).For each consensus statement,the result of the final vote and the grade of supporting evidence are given,followed by a discussion of key evidence.The statements have been separated into three categories of advice,(1)diet and exercise,(2)lifestyle and behaviour and(3)other interventions to target potential reflux-like symptom pathophysiology.The level of voting agreement achieved in each round is summarised in Figs.24.Diet and exercise adviceStatement 1:Identification and avoidance of specific die-tary triggers(e.g.citrus,tomatoes,highly spiced foods,fatty foods,fried foods and chocolate)should be recom-mended to individuals with postprandial reflux-like symp-toms.Agreement:100%(6,63.6%;5,36.4%;grade of evidence:D;strength of recommendation:high).Sixteen studies(one randomised crossover trial 13,one prospective cohort study 14,one before-after study 15,two case-control studies 16,17,eleven cross-sec-tional studies 1828)and two systematic reviews 29,30 supported the association of one or more dietary factors with reflux-like symptoms.The only study assessing a dietary intervention was a before-after study in patients presenting with reflux-like symptoms for the first time in primary care 15.Reflux-like symptoms decreased signif-icantly from baseline when patients were helped to iden-tify and fully/partially eliminate dietary triggers,and 45%of patients agreed to continue symptom management with dietary intervention alone 15.One cross-sectional study showing increased heartburn perception after ingestion of Advice for reflux-like symptom management Hungin et 3chili in patients with sleep disturbance(Pittsburgh Sleep Quality Index Score score 5)versus normal sleep 27,emphasizes how the impact of dietary triggers may be influenced by other lifestyle factors.Statement 2:Individuals who experience reflux-like symptoms after consuming alcoholic beverages should be advised to limit their intake of alcoholic beverages.Agreement:100%(6,72.7%;5,27.3%;grade of evi-dence:D;strength of recommendation:high).Seven studies(one RCT 31,one prospective cohort 14 and five cross-sectional 3236)and a meta-anal-ysis 37 support a positive association between alcohol Fig.1.Consensus procedure flow chart.Pilot statements and revisions are listed in Supplemental digital content 1,http:/ European Journal of Gastroenterology&HepatologyXXX XXX Volume XXX Number 00consumption and reflux-like symptoms.No interventional studies evaluating alcohol abstinence or reduction were identified.The meta-analysis by Pan et al.37 found a linear association between alcohol consumption and gas-tro-oesophageal reflux disease(GORD;diagnosed by the presence of oesophagitis or symptoms),with erosive reflux disease having a stronger association compared with non-erosive reflux disease(NERD).Statement 3:Individuals who experience reflux-like symptoms after consuming coffee should be advised to limit their intake of coffee.Agreement:100%(6,72.7%;5,27.3%;grade of evidence:C;strength of recommenda-tion:moderate).Five studies(two prospective cohort 14,38,two ran-domised crossover studies in coffee-sensitive individuals 39,40 and one cross-sectional study 41)support a posi-tive association between coffee consumption and reflux-like symptoms.However,a recent systematic review shows that the data are particularly conflicting,with multiple studies finding no increased risk of reflux-like symptoms in coffee drinkers 30.We did not identify any interventional stud-ies assessing the effect of reduced coffee intake on symp-toms.However,substitution analysis in the cohort study conducted by Mehta et al.38 showed that replacing two servings of coffee with water would reduce the risk of reflux-like symptoms hazard ratio(HR),096;95%confidence interval(CI),0.921.00 and a small,randomised study demonstrated significant symptom reduction and antacid use when coffee-sensitive individuals switched to dewaxed coffee(containing less caffeine and chlorogenic acids)39.Statement 4:Individuals who experience reflux-like symptoms after consuming carbonated beverages should be advised to limit their intake of carbonated beverages.Agreement:100%(6,72.7%;5,27.2%;grade of evi-dence:D;strength of recommendation:moderate).Eight studies(two prospective cohort 38,42,one case-control 16,and five cross-sectional 22,24,33,41,43)suggested that carbonated drinks are associated with an increase in reflux-like symptoms.The prospective cohort study conducted by Mehta et al.38 reported an increased risk of reflux-like symptoms(HR,1.29;95%CI,1.051.58;P 80%response to 2 weeks of PPI)suggesting acid-related aetiology was likely.Statement 7